Telmisartan is an angiotensin II receptor antagonist which is suitable for the treatment of high blood pressure and other medical indications as described in EP 502314 B1. The active substance has the following structure:

Telmisartan is generally prepared and sold in the form of the free acid. As disclosed in WO 00/43370, crystalline telmisartan occurs in two polymorphic forms which have different melting points. Under the influence of heat and moisture, the lower-melting polymorphic form B changes irreversibly into the higher-melting polymorphic form A.
Hitherto, telmisartan has been synthesized industrially by reacting 2-n-propyl-4-methyl-6-(1′-methylbenzimidazol-2′-yl)benzimidazole (I) with tert-butyl 4′-bromomethylbiphenyl-2-carboxylate (II) and subsequently saponifying according to the following Diagram 1.

The coupling by nucleophilic substitution in the first reaction step is described in general terms in EP 502314 B1 as process b), while the saponification of the tert-butyl ester group on a laboratory scale using trifluoromethylacetic acid is described in the patent specification as Example 1. Industrially, saponification has up till now been carried out with concentrated aqueous hydrobromic acid. Scaling up the method of synthesis known from the patent specification to a large-scale industrial process was surprisingly beset with problems. Thus, the active substance prepared by the process known up till now can only be obtained in a satisfactory quality after running through a number of process steps (the crude product does not have the required purity until it has been recrystallized twice), while very long centrifuging and drying times are needed when isolating the substance. The telmisartan synthesized on an industrial scale according to Diagram 1 is obtained after working up in the form of a product which has to be subjected to a second crystallization step to complete the purification. In the crystallization step, which is absolutely essential, the morphology of the end product crystallizing out led to unforeseen problems.
The product precipitated in the form of long needles is difficult to filter, wash, and isolate and, because of the inclusion of solvent, is also characterized by a very long drying time and forms large, very hard lumps during the drying process. Grinding up these lumps results in a dry powder which has a strong tendency to electrostatic charging and is virtually impossible to pour.
The abovementioned undesirable properties of a product have always proved to be a major obstacle to the large-scale production of a compound as they stop the product being manufactured reproducibly in large quantities and allow a high degree of purity to be achieved only with considerable difficulty or at additional high technical costs.
The aim of the present invention is therefore to provide an alternative method of preparing telmisartan, which can be used on a large scale and allows telmisartan to be easily worked up, purified, and isolated without the disadvantages mentioned above.